Complete antigen sequestration from the lymphoid organs is the prevailing but unproven mechanism of immunologic unresponsiveness to several unique tissue antigens that are capable of induction of organ-specific autoimmune diseases: myelin, lens proteins and sperm-specific antigens (SSA). With regards to SSA, circumstantial and direct evidence indicates the blood-testis barrier is incomplete, which implies that SSA may normally reach the peripheral lymphoid cells. Thus, active antigen-mediated immunoregulation must be seriously considered as a mechanism in the maintenance of immunologic unresponsiveness to SSA and in the prevention of autoimmune diseases involving the testis and sperm. In order to investigate this fundamental issue, we will first complete the isolation of three aspermatogenic antigens from guinea pig (GP) testis, establish sensitive and specific radioimmunoassays for their detection, and quantitate these antigens in the testicular and systemic venous blood and lymph of prepubertal and adult GP. Next, we will establish the experimental model whereby preimmunization of GP with aspermatogenic antigens with or without incomplete Freund's adjuvant prevents the induction of experimental allergic orchitis (EAO). By adoptive and passive transfer of lymphoid cells or serum from imbred and outbred GP that have been immunized with aspermatogenic antigens in incomplete Freund's adjuvant, we will determine the role of suppressor cells and/or suppressor serum factors in EAO prevention. The nature of suppressor cells will be determined with respect to antigenic specificity in immunosuppression, whether they are T or non-T lymphocytes, and whether they operate on the efferent arc of EAO induction. Finally, we will identify whether the suppressor serum factors are antibodies to aspermatogenic antigens of different immunoglobulin classes and/or immune complexes.